期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 50, 期 3-4, 页码 867-876出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2011.12.019
关键词
Chlorophyllin; Chemoprevention; Apoptosis; NF-kappa B; Survivin
资金
- Department of Biotechnology, New Delhi, India under Indo-EU
Chlorophyllin, a water-soluble, semi-synthetic derivative of the ubiquitous green pigment chlorophyll is shown to exert potent anticarcinogenic effects. In the present study, we investigated the chemopreventive effects of chlorophyllin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by analyzing the expression of NF-kappa B family members and markers of intrinsic apoptosis. Dietary administration of chlorophyllin (4 mg/kg bw) suppressed the development of HBP carcinomas by inhibiting the canonical NF-kappa B signaling pathway by downregulating IKK beta, preventing the phosphorylation of I kappa B-alpha, and reducing the expression of nuclear NF-kappa B. Inactivation of NF-kappa B signaling by chlorophyllin was associated with the induction of intrinsic apoptosis as evidenced by modulation of Bcl-2 family proteins, enforced nuclear localization of survivin, upregulation of apoptogenic molecules, activation of caspases, and cleavage of PARP. The results of the present study demonstrate that chlorophyllin inhibits the development of DMBA-induced HBP carcinogenesis by targeting NF-kappa B and the intrinsic apoptotic pathway. Thus, dietary agents such as chlorophyllin that simultaneously target divergent pathways of cell survival and cell death are novel candidates for cancer chemoprevention. (C) 2011 Elsevier Ltd. All rights reserved.
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